The present invention relates to a protected des-N-methylerythromycin derivative adapted for use as an intermediate for synthesis of chemically modified erythromycin derivatives.
Erythromycin A and erythromycin B are macrolide antibiotics obtainable through culture of streptomyces erythreus, and are represented by the following formula: ##STR1## wherein R=OH for erythromycin A; and
R=H for erythromycin B.
There have recently been made various attempts to improve the pharmaceutical effects through chemical modification of such erythromycins, such as methylation of the hydroxyl group in the 6- or 11-position of erythronolide or the hydroxyl group in the 4"-position of cladinose, as disclosed in the U.S. Pat. No. 4,331,803, E. Pat. No. 80,819 and U.S. Pat. No. 4,496,717.
In such chemical modification, in order to improve the selectivity of the reaction, it is necessary to protect the hydroxyl group in 2'-position or the amino group in 3-position, which are chemically active, as disclosed in the Japanese Patent Application Kokai Publication No. 58-92692.
However carbobenzoxy chloride (Z-cl) which has been widely employed as protecting agent is associated with certain drawbacks that benzyl alcohol, generated by the decomposition of said protecting agent, cannot be easily removed, and that said protecting agent is easily decomposable to significantly generate hydrogen chloride, thus inevitably leading to the decomposition of erythromycin.
In the course of a survey for resolving the drawbacks of such conventional technology, the present inventors have found that a stabler protected des-N-methylerythromycin derivative can be obtained by protecting 2'-hydroxyl and 3'-amino groups with 2-alkenyloxycarbonyl groups and protecting 9-position with a 2-alkenyloxyimino group and that all the protections can be removed in a one-pot reaction under a neutral condition, and thus have reached the present invention.